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Comparative integromics on FAT1, FAT2, FAT3 and FAT4.
1M&M Medical BioInformatics, Hongo 113-0033, Japan.
International Journal of Molecular Medicine
|July 26, 2006
Summary
This study determined the complete coding sequences for human FAT3 and FAT4, revealing novel conserved motifs and evolutionary divergence within the FAT family. These findings highlight FAT family members as potential targets in oncology and neurology.
Area of Science:
- Molecular Biology
- Genomics
- Cell Biology
Background:
- Planar cell polarity (PCP) signaling molecules, including WNTs and Cadherin superfamily members like FAT1-4, regulate crucial cellular processes.
- Previous research had incomplete coding sequences for human FAT3 and FAT4, hindering comprehensive analysis.
Purpose of the Study:
- To determine the complete coding sequences (CDS) for human FAT3 and FAT4.
- To analyze the domain architecture, identify conserved motifs, and perform phylogenetic analysis of the human FAT family.
- To investigate the expression patterns of FAT family members in various human tissues and cancers.
Main Methods:
- Bioinformatics and human intelligence (Humint) were employed to determine the complete CDS of human FAT3 and FAT4.
- Domain architecture comparison and phylogenetic analysis were conducted.
- mRNA expression analysis was performed across different tissues and cancer types.
Main Results:
- Complete CDS for human FAT3 and FAT4 were successfully determined.
- FAT3 encodes a 4557-aa protein and FAT4 encodes a 4924-aa protein, both with distinct Cadherin repeats, LamG, and EGF domains.
- Novel conserved cytoplasmic motifs (VCSVxPxLP and SDYxS) were identified in FAT1, FAT2, and FAT3 orthologs.
- Phylogenetic analysis indicated divergence between FAT1/FAT2/FAT3 and FAT4.
- FAT family mRNA expression was detected in various embryonic and adult tissues, including neural tissues and multiple cancer types (gastric, pancreatic, colorectal, breast, lung, ovarian, esophageal, skin, head and neck, prostate, brain tumors).
Conclusions:
- The complete CDS and detailed characterization of human FAT3 and FAT4 provide a foundation for understanding their functions.
- The identified conserved motifs and phylogenetic relationships offer insights into FAT protein evolution and function.
- The diverse expression patterns of FAT family members across normal tissues and cancers suggest their potential roles as targets in systems medicine for oncology and neurology.